adjuvant Abemaciclib in High risk HR+ EBC

2. monarchE Study Design
Johnstone S.et.al_ SABCS 2022

3. Overview of monarchE Data Cuts
Analysis Time points
Interim
Analysis1
Primary Outcome
(PO)
Additional Follow-
up 12 (AFU1)
Overall Survival Interim
Analysis
(OS IA2)
Date 16 March 2020 08 July 2020 01 April 2021 01 July 2022
Median Follow-up (months) 15.5 19.1 27.1 42.0
IDFS Events 323 395 565 835
Off Study Treatment* 26.4% 41.0% 89.6% 99.2%
 OS IA2 was planned to occur 2 years after the primary outcome analysis
 Follow up will continue to final OS analysis
Current Analysis
*0.8% of patients were randomized but never entered treatment period and are not included in these percentages
1Johnston SRD, et al. J Clin Oncol. 2020;38(34):3987-3998
2Harbeck* N, Rastogi* P, et al. Ann Oncol. 2021;32(12):1571-1581
*co-first authors
Johnston SD et.al_ SABCS 2022

4. IDFS Benefit in ITT Persists Beyond Completion of Abemaciclib
33.6% reduction in the risk of developing an IDFS event with an increase in absolute
benefit in IDFS 4-year rates (6.4%) compared to 2-and 3-year IDFS rates (2.8% and 4.8% respectively)
Johnston SD et.al_ SABCS 2022
OS IA2

5. *Region of enrollment and
Progesterone status data not shown
Consistent IDFS Benefit Observed in all Prespecified
Subgroups*
Johnston SD et.al_ SABCS 2022
OS IA2

6. DRFS Benefit in ITT Persists Beyond Completion of
Abemaciclib
34.1% reduction in the risk of developing a DRFS event with an increase in absolute
benefit in DRFS 4-year rates (5.9%), compared to 2-and 3-year rates (2.5% and 4.1%, respectively)
Johnston SD et.al_ SABCS 2022
OS IA2

7. Abemaciclib Treatment Benefit Deepened Over Time
aPiecewise hazard ratio as a post-hoc analysis was estimated using piecewise exponential model to assess the yearly treatment effect size;
b95% credible intervals were calculated by equal tails in the posterior samples of Bayesian exponential models
Johnston SD et.al_ SABCS 2022
OS IA2

8. OS Data Remain Immature in ITT
Number of OS events
Abemaciclib + ET ET Alone
157 173
HR (95% CI): 0.929 (0.748, 1.153)
Log-rank P = 0.5027
Fewer deaths (157 vs 173) were observed in the abemaciclib plus ET group versus the ET group
Johnston SD et.al_ SABCS 2022
OS IA2

10. Ki-67 is Prognostic, but Not Predictive of Abemaciclib
Benefit
Cohort 1*
C1 Ki-67 High C1 Ki-67 Low
Abemaciclib +
ET
N=1017
ET
alone
N=986
Abemaciclib
+ ET
N=946
ET alone
N=968
IDFS
Number of
events, n
147 224 91 141
HR (95% CI) 0.618 (0.501, 0.762) 0.624 (0.478, 0.814)
DRFS
Number of
events, n
126 193 74 119
HR (95% CI) 0.612 (0.488, 0.767) 0.613 (0.458, 0.821)
OS (Immature)
Number of
events, n
68 88 39 50
HR (95% CI) 0.733 (0.533, 1.007) 0.772 (0.506, 1.175)
*Ki-67 value was missing in 1203 (23.5%) patients
Within Cohort 1, similar abemaciclib treatment effects were observed regardless of Ki-67 index
Johnston SD et.al_ SABCS 2022
OS IA2

11. Efficacy Outcomes by Cohort
Cohort 2 enrolled patients with intermediate risk by clinicopathological features. Data remain immature
Cohort 1 Cohort 2
Abemaciclib + ET
N=2555
ET alone
N=2565
Abemaciclib + ET
N=253
ET alone
N=264
IDFS
Number of events, n 317 474 19 25
HR (95% CI) 0.653 (0.567, 0.753) 0.773 (0.420, 1.420)
Nominal p-value p<0.0001 p = 0.4048
4-yr IDFS rate, (95% CI)
85.5
(83.8, 87.0)
78.6
(76.7, 80.4)
NR NR
DRFS
Number of events, n 267 402 14 19
HR (95% CI) 0.652 (0.558, 0.761) 0.764 (0.383, 1.526)
Nominal p-value p<0.0001 p = 0.4448
4-yr DRFS rate, (95% CI)
87.9
(86.4, 89.3)
81.8
(79.9, 83.4)
NR NR
OS (Immature)
Number of events, n 147 168 10 5
HR (95% CI) 0.890 (0.714, 1.111) NR
NR: Not reported. Low event number does not allow reliable statistical analysis.
Johnston SD et.al_ SABCS 2022
OS IA2

14. monarchE
Subgroup analysis by menopausal status

15. IDFS By Menopausal Status
Kaplan-Meier plot of invasive disease-free survival by menopausal status [interaction p value = 0.082]4
a. Premenopausal b. Postmenopausal
Treatment benefit was consistent in both premenopausal and postmenopausal subgroups
Paluch-Shimon S. et.al_ ESMO BC 2022
AFU1

16. DRFS By Menopausal Status
Kaplan-Meier plot of distance relapse-free survival by menopausal status [interaction p value = 0.137]4
a. Premenopausal b. Postmenopausal
Treatment benefit was consistent in both premenopausal and postmenopausal subgroups
Paluch-Shimon S. et.al_ ESMO BC 2022
AFU1

17. Endocrine therapy treatments by menopausal status
dET and GnRH use were well balanced between treatment arms as presented at ESMO 20211
eMedian age 45, 94.9% patients received prior chemotherapy
Summary of endocrine treatments by menopausal status based on physician’s choice
Paluch-Shimon S. et.al_ ESMO BC 2022
AFU1

18. Efficacy Results for Premenopausal Patients Based Upon
Endocrine Therapy
Efficacy results for preM patients by endocrine therapy subgroups
Interaction test p-value: 0.350 for IDFS and 0.335 for DRFS
Paluch-Shimon S. et.al_ ESMO BC 2022
AFU1

19. From Bench to Bedside
Risk Assessment in HR+, HER2-, EBC &
Who should receive CDK 4/6 inhibitor?

20. 1. What clinical and pathological parameters will you use to
define high-risk recurrence for HR+, HER2- early breast cancer
(EBC) patients?
A. Node status
B. Tumor size
C.Tumor grade
D.Ki67
E. Menopausal status
F. Age
G.Response to Neoadjuvant chemotherapy
H.Other (e.g. Multigene assay, online staging tool, etc.)

21. 2. A 65 Y/O female, postmenopause, HR+, HER2- EBC, s/p Mastectomy +
axillary LN dissection, 4 LN+, Tumor size 3 cm, Grade 2 , Ki67 : 30%, after
adjuvant chemotherapy with TC x 4 , Which adjuvant endocrine treatment
would you consider :
A. AI
B. AI + Abemaciclib
C.others

22. 3. A 45 Y/O female, premenopause, HR+, HER2- EBC, s/p partial mastectomy +
axillary LN dissection, 4 LN+, Tumor size 2.5cm, Grade 1, Ki67 : 20%, after
adjuvant chemotherapy with EC x 4 + Taxotere x 4, Which adjuvant endocrine
treatment would you consider :
A. Tamoxifen
B. LHRHa + Tamoxifen / AI
C.Tamoxifen + Abemaciclib
D.LHRHa + Tamoxifen / AI + Abemacilib
E. others

23. 4. A 65 Y/O female, postmenopause, HR+, HER2- EBC, s/p Mastectomy +
axillary LN dissection, 1 LN+, Tumor size 5 cm, Grade 1 , Ki67 : 10%, after
adjuvant chemotherapy with TC x 4, Which adjuvant endocrine treatment
would you consider :
A. AI
B. AI + Abemaciclib
C.others

24. 5. A 45 Y/O female, premenopause, HR+, HER2- EBC, s/p partial mastectomy +
axillary LN dissection, 1 LN+, Tumor size 2 cm, Grade 3, Ki67 : 40%, after
adjuvant chemotherapy with EC x 4 + Taxotere x 4, Which adjuvant endocrine
treatment would you consider :
A. Tamoxifen
B. LHRHa + Tamoxifen / AI
C.Tamoxifen + Abemaciclib
D.LHRHa + Tamoxifen / AI + Abemacilib
E. others

25. 6. A 65 Y/O female, postmenopause, HR+, HER2- EBC, s/p Mastectomy +
axillary LN dissection, 3 LN+, Tumor size 4 cm, Grade 2 , Ki67 : 50%, patient
refused any adjuvant chemotherapy, Which adjuvant endocrine treatment
would you consider :
A. AI
B. AI + Abemaciclib
C.others

26. 7. A 65 Y/O female, postmenopause, HR+, HER2- EBC, cT2cN2M0, post
neoadjuvant C/T with EC x 4 + Taxotere x 4, s/p partial mastectomy + axillary LN
dissection, 1 LN+, Tumor size 0.5 cm, Grade 3, Ki67 : 50%, Which adjuvant
endocrine treatment would you consider :
A. AI
B. AI + Abemaciclib
C.others

27. 8. A 45 Y/O female, premenopause, HR+, HER2- EBC, cT2cN2M0, post
neoadjuvant C/T with EC x 4 + Taxotere x 4, s/p mastectomy + axillary LN
dissection, 3 LN+, Tumor size 4 cm, Grade 1, Ki67 : 20%, Which adjuvant
endocrine treatment would you consider :
A. Tamoxifen
B. LHRHa + Tamoxifen / AI
C.Tamoxifen + Abemaciclib
D.LHRHa + Tamoxifen / AI + Abemacilib
E. others

28. 9. After such warm-up & Q/A program, how much are you confident at using
Abemacicilb in your daily practice :
A. Very confident
B. Slight confident
C.Not so confident
D.Not confident at all